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Biomedical subjects

M Epstein

Publications and source records attributed to M Epstein.

At least 19 recordsLinked to original sources
PubMed2000

Joint contact mechanics in the early stages of osteoarthritis.

Joint degeneration in the early stages of osteoarthritis (OA) may be reflected in changes in structural and material properties in articular cartilage. The aim of the present study was to simulate numerically the contact area and stress distribution in normal and "diseased" cartilage layers for dynamic loading. The initial stages of osteoarthritis were simulated based on an experimental model: the anterior cruciate ligament-transected cat knee. In this model, cartilage layers become thicker, softer, and more permeable than the corresponding healthy cartilage layers within weeks of intervention. In our numerical simulations, the diseased cartilage was modelled by changing the thickness, permeability, shear modulus, and Poisson's ratio of the cartilage in accordance with observations in this experimental model of osteoarthritis. The theoretical model of normal and diseased articular cartilage was based on a biphasic representation of cartilage, and the joint was assumed to be axi-symmetric. It was found that, for a given loading condition, the contact areas increase and peak stresses decrease in the diseased compared to the normal joint. According to our simulations, areas of normal joint contact become unloaded and areas of little or no contact become overloaded in the early stages of osteoarthritis compared to the situation in normal joints. Based on these results, we speculate that OA may be initiated following ACL transection because of an overloading of specific regions of the joint, either because of the altered contact mechanics or the disrupted joint stability, despite a general decrease in the contact pressure.

Animals↗
PubMed2000

Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group.

Over 11 million Americans have both diabetes and hypertension-comorbid diseases that strongly predispose people to both renal as well as cardiovascular (CV) injury. Hypertension substantially contributes to CV morbidity and mortality in people with diabetes. Diabetes is the most common cause of end-stage renal disease in the United States. Furthermore, hypertension and diabetes are particularly prevalent in certain populations, such as African-Americans and Native Americans. Since the 1994 Working Group Report on Hypertension and Diabetes, a large body of clinical trial data has affirmed the original blood pressure goal of less than 130/85 mmHg recommended to preserve renal function and reduce CV events in people with hypertension and diabetes. Data that are more recent have emerged, however, to support an even lower diastolic blood pressure goal, ie, 80 mmHg, in order to optimally preserve renal function and reduce CV events in people with diabetic nephropathy. A review of clinical trials indicates that more than 65% of people with diabetes and hypertension will require two or more different antihypertensive medications to achieve the new suggested target blood pressure of 130/80 mmHg. The purpose of this report is to update the previous recommendations with a focus on level of blood pressure control, proteinuria reduction, and therapeutic approaches to achieve these goals. We provide an evidence-based approach, integrating data from the major clinical trials that were designed as randomized prospective, long-term studies that had as a primary endpoint either progression of diabetic nephropathy or reduction in CV events. This report also addresses socioeconomic and cultural barriers that hinder achievement of blood pressure goals. Lastly, the report discusses approaches to resolve cultural barriers, both physician- and patient-derived, that interfere with achievement of lower blood pressure goals.

Adult↗
PubMed2000

Hypertension in patients with diabetes. Why is aggressive treatment essential?

Hypertension and diabetes are interrelated diseases. Alone, each condition is a risk factor for cardiovascular disease and, together, they strongly predispose to end-stage renal disease, coronary artery disease, and peripheral vascular and cerebrovascular disease. Pharmacologic treatment of hypertension can substantially reduce morbidity and mortality in diabetic patients with hypertension, but adequate control of blood pressure is seldom achieved in a clinical setting. More aggressive treatment is needed to improve the prognosis for this over-expanding patient population.

Antihypertensive Agents↗
PubMed2000

Hypertension in patients with diabetes. Strategies for drug therapy to reduce complications.

Hypertension in diabetic patients must be treated aggressively if patients are to benefit from reduced risk of morbidity and mortality. Diabetes itself must be diagnosed promptly, particularly in at-risk patients, so appropriate lifestyle modifications can be made at the earliest opportunity. Although this may reduce or delay onset of hypertension, antihypertensive drug treatment should be initiated in the diabetic patient with even high-normal blood pressure. Traditional approaches to management of hypertension are inappropriate for most patients with diabetes. While ACE inhibitors, calcium antagonists, angiotensin II receptor blockers, beta blockers, and low-dose diuretics, alone or in combination, all currently have roles in hypertension management, the outcomes of studies now under way may clarify some still unanswered questions about the dangerous combination of high blood pressure and diabetes.

Diabetes Complications↗
PubMed1999

Current strategies for management of hypertensive renal disease.

The incidence of hypertensive end-stage renal disease continues to increase annually. To reduce this incidence, it is necessary to control systolic and diastolic hypertension. Reversible causes should always be sought in any hypertensive patient who develops renal insufficiency. Blood pressure should be reduced to 130/85 mm Hg, and in African Americans with hypertensive renal failure, reducing the blood pressure to 120/75 mm Hg may be beneficial. Any antihypertensive treatment regimen that effectively lowers blood pressure will help slow progressive renal failure. Whenever possible, an angiotensin-converting enzyme inhibitor should be part of the treatment, since these drugs have been shown to be renoprotective beyond their antihypertensive effect in certain renal disease categories.

Antihypertensive Agents↗
PubMed1999

Improved solution for solitary waves in arteries.

Nonlinear waves are investigated numerically by a direct analysis of the field equations, thereby establishing the magnitude of the errors inherent in the commonly used reductive perturbation technique. The method is also applied beyond the long-wave approximation and a comparative assessment of the results obtained is presented.

Arteries↗
PubMed1999

Modelling of location- and time-dependent deformation of chondrocytes during cartilage loading.

Experimental evidence suggests that the biosynthetic activity of chondrocytes is regulated primarily by the mechanical environment. In order to study the mechanisms underlying remodeling, adaptation, and degeneration of articular cartilage in a joint subjected to changing loads, it is important to know the time-dependent fluid pressure and stress-strain state in chondrocytes. The purpose of the present study was to develop a theoretical model to simulate the mechanical behaviour of articular cartilage and to describe the time-dependent stress-strain state and fluid pressure distribution in chondrocytes during cartilage deformation. It was assumed that the volume occupied by the chondrocytes is small and that cartilage can be treated as a macroscopically homogenized material with effective material properties which depend on the material properties of the cells and matrix and the volumetric fraction of the cells. Model predictions on the time-dependent distribution of fluid pressure and stress and on the time-dependent cell deformation during confined and unconfined compression tests agree with previous theoretical predictions and experimental observations. The proposed model supplies the tools to study the mechanisms of degeneration, adaptation and remodelling of cartilage associated with cell loading and deformation.

Adaptation, Physiological↗
PubMed1999

Fenoldopam: a new parenteral antihypertensive: consensus roundtable on the management of perioperative hypertension and hypertensive crises.

A panel of clinicians from anesthesiology, surgery, nephrology, hypertension, cardiology, and pharmacology was convened to discuss pharmacologic therapeutics in the management of hypertensive crisis and perioperative hypertension. The panel discussed the advantages and limitations of currently available parenteral drugs, and assessed the potential use of fenoldopam mesylate, a drug in clinical development since 1981, and recently approved by the U.S. Food and Drug Administration (FDA). Fenoldopam is a dopamine receptor (DA1 selective) agonist that is a systemic and renal vasodilator. It was concluded that fenoldopam offers significant advantages as a parenterally administered agent for the management of blood pressure in both hypertensive emergencies and in the perioperative setting.

Acute Disease↗
PubMed1999

Diagnosis and management of hypertensive emergencies.

It has been estimated that approximately 600,000 to 800,000 Americans will develop a hypertensive crisis (Calhoun and Oparil, 1990). Although such numbers represent only about 1% of the estimated 60 million Americans with hypertension, hypertensive crisis often constitutes a major medical emergency, necessitating a focused, assertive, and reasoned therapeutic intervention. When such patients are seen in the emergency department or in a physician's office with a critical elevation in blood pressure (BP), appropriate and efficacious management is essential to avoid catastrophic injury to vital target organs, including the central nervous system, the heart, and the kidneys. Delays in initiating effective therapy or, equally important, overzealous therapy leading to a too-rapid reduction in BP can produce severe complications involving these target organs. This article reviews the spectrum of clinical syndromes that comprise hypertensive emergencies, highlighting 2 to illustrate the complexities of clinical presentation and management. The newly advocated treatment guidelines based on the category of acute severe hypertension (including asymptomatic hypertensive urgencies) are also considered, as are therapeutic strategies utilizing currently available antihypertensive agents.

Adrenergic alpha-Agonists↗
PubMed1999

Subclinical depletion of primordial follicular reserve in mice treated with cyclophosphamide: clinical importance and proposed accurate investigative tool.

Studies have shown that ovarian failure is a common side-effect of chemotherapy treatment; however, continuation of regular menses post-treatment does not necessarily imply that the ovaries have escaped damage. This animal study measures directly the primordial follicle (PMF) loss following exposure to chemotherapy and evaluates reproductive outcome following significant destruction of the PMF population. Inbred Balb/c mice aged 5-6 weeks were administered different doses of an alkylating agent, cyclophosphamide, and the total number of PMF remaining in both ovaries was counted. Results show that cyclophosphamide causes PMF destruction in proportion to increasing dose (P = 0.0001). Reproductive performance was assessed after exposure to 75 mg/kg cyclophosphamide, a dose which destroys approximately 50% of PMF reserve, by evaluation of ovulation, mating and pregnancy rates. Reproductive potential of treated mice was not affected compared with controls despite the significant loss of PMF. Our results indicate that reproductive performance is not an accurate parameter for assessing ovarian injury. Rather, histological counting of PMF number more directly reflects the damage caused by chemotherapy to the ovary. This method can be used as a sensitive, inexpensive tool to gauge the damage to fertility caused by new chemotherapy agents or protocols.

Animals↗
PubMed1999

The effects of fenoldopam, a selective dopamine receptor agonist, on systemic and renal hemodynamics in normotensive subjects.

OBJECTIVE: Acute renal failure, frequently a consequence of renal vasoconstriction and subsequent renal ischemia, is a common problem for which no proven preventive or therapeutic agents exist. Fenoldopam is a new, selective, dopamine-1 receptor agonist that causes both systemic and renal arteriolar vasodilation. In hypertensive patients, fenoldopam rapidly decreases blood pressure, increases renal blood flow, and maintains or improves the glomerular filtration rate. We sought to determine a dose of fenoldopam that increases renal blood flow without inducing hypotension in normotensive patients and to explore the role of volume status (sodium replete vs. deplete) in these effects. DESIGN: Randomized, double-blind, placebo-controlled, cross-over study. SETTING: Clinical research unit. PATIENTS: Fourteen normal male volunteers. INTERVENTIONS: Renal plasma flow (para-aminohippurate clearance) and glomerular filtration rate (inulin clearance) were measured during three fixed, escalating doses of fenoldopam (0.03, 0.1, and 0.3 Lg/kg/min) on both a high-sodium and a low-sodium diet. MEASUREMENTS AND MAIN RESULTS: Fenoldopam significantly increased renal plasma flow in a dose-dependent manner compared with placebo: 670 + 148 vs. 576 + 85 mUmin at 0.03 iLg/kg/min; 777 + 172 vs. 579 + 80 mUmin at 0.1 tig/kg/min; and 784 + 170 vs. 592 + 165 mUmin at 0.3 ilg/kg/min (p < .05 fenoldopam vs. placebo at all three doses). Glomerular filtration rate was maintained. At the lowest dose (i.e., 0.03 ILg/kg/min), significant renal blood flow increases occurred without changes in systemic blood pressure or heart rate. At 0.1 and 0.3 Lgl/kg/ min, systolic blood pressure did not change, but diastolic blood pressure was slightly lower in the fenoldopam group than in the placebo group: 62.5 + 6.4 vs. 63.6 + 2.6 mm Hg, respectively, at 0.3 tg/kg/min (p < .05). None of the effects of fenoldopam were altered by volume status. CONCLUSIONS: Fenoldopam increased renal blood flow in a dose-dependent manner compared with placebo, and, at the lowest dose, significantly increased renal blood flow occurred without changes in systemic blood pressure or heart rate. These findings will be useful in designing future studies exploring the role of fenoldopam in preventing or treating renal failure in patients who are not hypertensive.

Acute Kidney Injury↗
PubMed1999

Role of a third generation calcium antagonist in the management of hypertension.

Calcium antagonists are uniquely suitable for managing hypertension by virtue of their efficacy, metabolic neutrality and their ability to countervail counterregulatory adaptive changes, thereby enhancing blood pressure lowering. Recent evidence has accrued underscoring the concept that calcium antagonists are heterogeneous and consist of chemically dissimilar agents. The difference in formulations and pharmacokinetics affect clinical events including the effect on blood pressure, heart rate and the degree with which sympathetic activity is activated. Lacidipine is a new calcium antagonist that is the prototype of the lipophilic dihydropyridines. Of great importance, lacidipine has a slow onset of vasodilator/antihypertensive effect and does not promote an excessive sympathetic drive. These attributes commend its selection as an antihypertensive agent.

Antihypertensive Agents↗
PubMed1999

Lysophosphatidic acid and mesangial cells: implications for renal diseases.

The last decade has witnessed a phenomenal increase in our understanding of the biological role of lysophosphatidic acid (LPA) and has led to an appreciation of this critical serum-derived growth factor released from platelets. We herein summarize recent observations that collectively support the hypothesis that LPA may play a key role in the pathogenesis of initiation and progression of proliferative glomerulonephritis. LPA synergistically stimulates mesangial cell proliferation in combination with platelet-derived growth factor in primary culture. The mechanism of co-mitogenesis is likely to be mediated by the prolonged activation of mitogen-activated protein kinase which is stimulated by platelet-derived growth factor and LPA through different mechanisms. LPA contracts cultured mesangial cells and has properties in common with other pressor molecules including mobilization of intracellular Ca2+ and promotion of Ca2+ entry through dihydropyridine-sensitive calcium channels. LPA receptor mRNA has been identified in isolated glomeruli dissected from renal biopsy samples of patients with IgA nephropathy. All of these facts have led us to postulate that LPA is produced within glomeruli and that LPA's mitogenic as well as haemodynamic action contribute to the pathological process of mesangial proliferative glomerulonephritis. The possible production of LPA as an autocrine factor from mesangial cells themselves has also been discussed.

Glomerular Mesangium↗
PubMed1998

Evaluation of the finite element software ABAQUS for biomechanical modelling of biphasic tissues.

The biphasic cartilage model proposed by Mow et al. (1980) has proven successful to capture the essential mechanical features of articular cartilage. In order to analyse the joint contact mechanics in real, anatomical joints, the cartilage model needs to be implemented into a suitable finite element code to approximate the irregular surface geometries of such joints. However, systematic and extensive evaluation of the capacity of commercial software for modelling the contact mechanics with biphasic cartilage layers has not been made. This research was aimed at evaluating the commercial finite element software ABAQUS for analysing biphasic soft tissues. The solutions obtained using ABAQUS were compared with those obtained using other finite element models and analytical solutions for three numerical tests: an unconfined indentation test, a test with the contact of a spherical cartilage surface with a rigid plate, and an axi-symmetric joint contact test. It was concluded that the biphasic cartilage model can be implemented into the commercial finite element software ABAQUS to analyse practical joint contact problems with biphasic articular cartilage layers.

Animals↗
PubMed1998

Can a rheological muscle model predict force depression/enhancement?

A new phenomenological model of activated muscle is presented. The model is based on a combination of a contractile element, an elastic element that engages upon activation, a linear dashpot and a linear spring. Analytical solutions for a few selected experiments are provided. This model is able to reproduce the response of cat soleus muscle to ramp shortening and stretching and, unlike standard Hill-type models, computations are stable on the descending limb of the force-length relation and force enhancement (depression) following stretching (shortening) is predicted correctly. In its linear version, the model is consistent with a linear force-velocity law, which in this model is a consequence rather than a fundamental characteristic of the material. Results show that the mechanical response of activated muscle can be mimicked by a viscoelastic system. Conceptual differences between this model and standard Hill-type models are analyzed and the advantages of the present model are discussed.

Algorithms↗
PubMed1998

Material and functional properties of articular cartilage and patellofemoral contact mechanics in an experimental model of osteoarthritis.

The purposes of this study were to determine the in situ functional and material properties of articular cartilage in an experimental model of joint injury, and to quantify the corresponding in situ joint contact mechanics. Experiments were performed in the anterior cruciate ligament (ACL) transected knee of the cat and the corresponding, intact contralateral knee, 16 weeks following intervention. Cartilage thickness, stiffness, effective Young's modulus, and permeability were measured and derived from six locations of the knee. The total contact area and peak pressures in the patellofemoral joint were obtained in situ using Fuji Pressensor film, and comparisons between experimental and contralateral joint were made for corresponding loading conditions. Total joint contact area and peak pressure were increased and decreased significantly (alpha=0.01), respectively, in the experimental compared to the contralateral joint. Articular cartilage thickness and stiffness were increased and decreased significantly (alpha=0.01), respectively, in the experimental compared to the contralateral joint in the four femoral and patellar test locations. Articular cartilage material properties (effective Young's modulus and permeability) were the same in the ACL-transected and intact joints. These results demonstrate for the first time the effect of changes in articular cartilage properties on the load transmission across a joint. They further demonstrate a substantial change in the joint contact mechanics within 16 weeks of ACL transection. The results were corroborated by theoretical analysis of the contact mechanics in the intact and ACL-transected knee using biphasic contact analysis and direct input of cartilage properties and joint surface geometry from the experimental animals. We conclude that the joint contact mechanics in the ACL-transected cat change within 16 weeks of experimental intervention.

Animals↗